Sleep disordered breathing is commonly treated with positive airway pressure therapy. Positive airway pressure therapy is delivered via a tight-fitting mask with common side effects including: leak, ineffective treatment, residual sleep disordered breathing, eye irritation, nasal congestion, pressure ulcers and poor concordance with therapy. This systematic review and meta-analysis aimed to identify the effectiveness of current treatment strategies for managing side effects associated with positive airway pressure therapy. Five databases were searched and 10,809 articles were screened, with 36 articles included in the review. Studies investigated: dressings, nasal spray/douche, chin straps, heated humidification and interfaces. No intervention either improved or detrimentally affected: positive airway pressure concordance, Epworth Sleepiness Score, residual apnoea hypopnea index or interface leak. The review was limited by study heterogeneity, particularly for outcome measures. Additionally, patient demographics were not reported, making it difficult to apply the findings to a broad clinical population. This review highlights the paucity of evidence supporting treatment strategies to manage side effects of positive airway pressure therapy.